Pulmonary circulation is one of low resistance, about one-eighth of systemic blood pressure. Pulmonary hypertension is caused largely by an increase in pulmonary vascular resistance and is classified clinically as either primary or secondary. Secondary pulmonary hypertension, the more common form, is generally a result of (1) chronic obstructive or interstitial lung disease; (2) recurrent pulmonary emboli; (3) liver disease; or (4) antecedent heart disease. Primary pulmonary hypertension is diagnosed only after all known causes of increased pulmonary pressure are excluded.
Plexogenic pulmonary hypertension is a histological definition identified by the presence of plexiform lesions, concentric luminal proliferation, and fibrinoid necrosis within the pulmonary vasculature. These lesions are characteristic of primary pulmonary hypertension and secondary pulmonary hypertension, e.g., associated with congenital cyanotic heart disease and hepatic cirrhosis.
Untreated pulmonary hypertension leads to progressive cor pulmonale with right ventricular hypertrophy and strain, and subsequently a pulmonary crisis develops with decompensated right heart failure. The prognosis for patients with pulmonary hypertension is poor, with a median survival time of 2.3 years from diagnosis.
Within the lungs exists an autonomous endocrine system, termed the pulmonary neuroendocrine system (PNES). This system has been shown to secrete the humoral peptides calcitonin and bombesin-like peptide, e.g., gastrin related peptide (GRP). However, neither bombesin nor GRP, under a wide range of experimental conditions, have any demonstrable in vivo pulmonary haemodynamic effect. Additionally, bombesin was shown not to have an effect on isolated pulmonary arteries. Furthermore, it has not been reported that a bombesin antagonist is capable of lowering the pulmonary blood pressure of a patient.